Let Those Without Syn Cast the First Post

Let Those Without Syn Cast the First Post

Author: David Bradley

Increasing Openness in Science

If you are publishing the chemical recipes for your organic syntheses, then you had better be on the mark when it comes to the specifics, the yields, and the side products. Why? Because the bloggers are watching!

Science has for many years been about reproducibility, and rightly so. There is little merit in an experiment that is a one-off – Large Hadron Colliders the exception – if no one else can replicate your tests and get the same data at the end of it. But, one wonders how many hundreds, if not thousands of papers have been through the peer-review process and come out the other side ready to collect their citations without anyone else ever having raised a test-tube in their honor?

Of course, there has been replication of experiments in some cases. An important result warrants testing and practical preparations would inevitably be put under pressure to perform. There have been retractions over the years, but in the past these have moved on an almost geological timescale. Today, bloggers have come to represent a new catalyst for change.

Most readers will be well aware of the controversy surrounding research on allegedly arsenic-munching microbes [1] published in 2010 in the highly prestigious journal Science and subsequently retracted for being “incorrect in some of its major findings” as the Washington Post put it [2].

It was the initial discussions in the blogosphere that brought the story to a head early on. This increasing openness and ability to scrutinize results and critique a scientist’s data in public perhaps has its logical lead in the efforts of Jean-Claude Bradley of Drexel University, Philadelphia, Pennsylvania, USA, and a growing number of other scientists who would like to see open notebook science become the norm rather than an oddity.

Public Reproducibility

An intriguing recent example of this new awareness shows how the process can work both ways. In January, the website Blog Syn was started by volunteers. It describes itself as “crowdsourcing meets organic synthesis” and carries out a kind of reaction check. In February, Blog Syn highlighted a fairly old synthetic scheme by Phil Baran, K. C. Nicolaou et al., Scripps Research Institute, La Jolla, California, USA, published in the Journal of the American Chemical Society (JACS) more than a decade ago [3].

The reaction involved is a benzylic oxidation and was one of a series providing a toolkit for organic chemists highlighting the uses of o-iodoxybenzoic acid (IBX, pictured) in organic synthesis. Unfortunately, it seemed the reaction in that paper was to say the least “difficult to reproduce” [4]. Some attempts by chemists obtained very low, if any yield.

I spoke to anonymous chemistry blogger, See Arr Oh, a pharmaceutical chemist active on Blog Syn, on behalf of ChemViews magazine. They had this to say: “First, [there are] no witch-hunts or vindictive sentiments behind our chemistry; we hope only to further the chemistry and make all these great reactions work properly in others’ hands.”

I did not imagine that there was any malice in the efforts of Blog Syn, and thankfully, the story of the JACS paper does not end badly. Instead, we see the original author, Phil Baran, offer some assistance. He apparently carried out his original experiment again, obtained good yields and sent the bloggers a much more detailed write-up so that they might do the same. In his response, Baran, tells the bloggers that, “Your blog will remind the community of the importance of documenting even the most minute and subtle details and pictures of reaction setups of new reactions.”

The inimitable Derek Lowe of Corante’s In the Pipeline blog, himself an organic chemist in the pharmaceutical industry with not inconsiderable experience of reactions, reaffirms my earlier point that science is about reproducibility and congratulates Baran for his response while at the same time telling us that public reproducibility is an idea whose time has come [5].

Science in the Digital Age

In the digital age, there are no page lengths to worry about, storage is almost infinite, there is the possibility of easily publishing full experimental details somewhere accessible without having to worry about whether or not an editor thinks they are necessary or should be left out of even the supplementary data. Whether or not open notebook science comes entirely to the fore is a different matter, not all scientists want to publish every blotchy and often stinky page of their lab books for all to see. Conversely, I suspect that the majority of referees would not want to have to wade through every such lab book and certainly not have to attempt to reproduce every procedure in a paper they are sent for review before they can come to a publish-or-be-damned conclusion.

Science itself is not changing. Science is about observation, testing, corroboration, refutation, and presumably always will be. What is changing are some of the tools it uses in those endeavors. Drexel’s Bradley told ChemViews magazine that he feels that, “it is very important to stick to objective reporting – if results don’t match those reported by others it is important to remove all emotion and just report that as an observation.” He adds that he is very encouraged by the increasing numbers of organic chemists who are becoming more open.

Meanwhile, the authors at Blog Syn wrapped up the IBX topic recently with a thank you to Baran and his colleagues Tamsyn Montagnon and Yong-Li Zhong “for engaging us honestly and professionally, and helping uncover some of the hidden factors that make this reaction work.” Apparently, a splash of water was all that was needed to make things work perfectly well [6]. As with a really good single malt whiskey, or fruit cordial if you prefer, a dash of water can make all the difference.

[1] Do As Bacteria Exist?, ChemistryViews.org 2010, December 09. Link

[2] Marc Kaufman, Journal retreats from controversial arsenic paper, Washington Post 2012, July 08. Link

[3] Iodine(V) Reagents in Organic Synthesis. Part 4. o-Iodoxybenzoic Acid as a Chemospecific Tool for Single Electron Transfer-Based Oxidation Processes, K. C. Nicolaou, T. Montagnon, P. S. Baran, Y. L. Zhong, J. Am. Chem. Soc. 2002, 124, 2245–2258. DOI: 10.1021/ja012127+

[4] Blog Syn #003: Benzylic Oxidation of Arylmethanes by IBX, Blog Syn 2013February 18. Link

[5] Derek Lowe, Phil Baran at Blog Syn, In The Pipeline 2013, February 26. Link

[6] Blog Syn #003A: Secret Ingredient, Blog Syn 2013, March 03. Link

Also of interest:

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